Lung CancerCLEVERNCT06079970
Confocal Laser Endomicroscopy VERification
A study testing Neelde Based Confocal Laser Endomicroscopy and Conventional diagnostic bronchoscopy in people with Lung Cancer and Lung Neoplasm Malignant, run by Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC) at 5 sites in 5 countries.
Trial summary
The goal of this multi-center randomized clinical trial is to evaluate the added value of needle based confocal laser endomicroscopy (nCLE)-imaging to regular diagnostic bronchoscopic peripheral lung lesion analysis on the diagnostic yield in patients with peripheral pulmonary nodules suspect for malignancy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Lung Neoplasm Malignant, Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Neelde Based Confocal Laser Endomicroscopy and Conventional diagnostic bronchoscopy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 18 Oct 2023to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years of age
- Suspected malignant peripheral lung lesion with an indication for a bronchoscopic diagnostic work-up as determined by the attending physician or tumor board. Peripheral pulmonary lesions are defined as lesions located beyond the visible segmental bronchi, not detectable by regular flexible bronchoscopy
- Bronchus sign on pre-procedural CT or estimated confidence for successful navigation to the nodule resulting in a r-EBUS signal
- Solid part of the lesion must be ≧10 mm
- Largest dimension of lesion size on CT ≦30 mm (long-axis)
- Ability to understand and willingness to sign a written informed consent
Who cannot join
- Inability or non-willingness to provide informed consent
- Endobronchial visible malignancy on bronchoscopic inspection
- Target lesion within reach of the linear EBUS scope
- Failure to comply with the study protocol
- Known allergy or risk factors for an allergic reaction to fluorescein
- Pregnancy or breastfeeding
Show all 11Show fewer
- Hemodynamic instability
- Refractory hypoxemia
- Therapeutic anticoagulant use that cannot be withheld for an appropriate interval before the procedure
- Unable to tolerate general anesthesia according to the anesthesiologist
- Undergoing chemotherapy as several chemotherapies have fluorescent properties at the same wavelength (e.g., doxorubicin)
Trial locations and contacts
5 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
Jouke Annema, Prof. dr. contact
5 sites in 5 countries
United States1 site, 1 recruiting
- Recruiting
Montefiore Medical Center
New York, New York, 10467
Ali Sadoughi, MD, DAABIP
Ali Sadoughi, MD, DAABIP
Austria1 site, 1 recruiting
- Recruiting
Vienna General Hospital
Vienna
Daniela Gompelmann, Prof.
Daniela Gompelmann
Czechia1 site, 1 recruiting
- Recruiting
General University Hospital Prague
Prague
Zuzana Šestáková
Jirí Votruba
Greece1 site, 1 recruiting
- Recruiting
Sotiria Hospital
Athens
Grigoris Stratakos, MD, PhD
Nektarios Anagnostopoulos
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam University Medical Centers
Amsterdam, 1081 HV
Saskia van Heumen, MSc
Jouke Annema, Prof. dr.
About this study
Official title: Bronchoscopy With and Without Needle-based Confocal Laser Endomicroscopy for Peripheral Lung Nodule Diagnosis: Protocol for a Multicenter Randomized Controlled Trial (CLEVER Trial)
The goal of this multi-center randomized clinical trial is to evaluate the added value of needle based confocal laser endomicroscopy (nCLE)-imaging to regular diagnostic bronchoscopic peripheral lung lesion analysis on the diagnostic yield in patients with peripheral pulmonary nodules suspect for malignancy.
The main question[s] it aims to answer are:
Read more
To determine if the addition of nCLE-imaging to conventional diagnostic bronchoscopic peripheral lung lesion analysis results in an improved diagnostic yield (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis out of the total number of patients that have received the diagnostic bronchoscopic procedure).
Participants will undergo diagnostic bronchoscopy either with or without the addition of nCLE imaging before each TBNA. Based on the feedback of the CLE images on (in)correct placement of the needle, the needle might be repositioned before sampling. Comparison between the diagnostic yield of these groups will be done including subgroup analysis.
Read the detailed description
Rationale: Lung cancer screening and the increasing use of chest-computed tomography (CT) has led to an increase in the number of (incidental) found suspected malignant lung lesions. Since tissue acquisition for pathological analysis is prerequisite for diagnosis and optimal treatment, a drastic increase in the number of patients that need to undergo bronchoscopy is expected.
Over 70% of the suspected lesions develop in the periphery of the lung and are therefore not visible during conventional bronchoscopy. Although several bronchoscopic navigational techniques demonstrated an improved navigation towards the target lesion, the diagnostic yield remains suboptimal due to a substantial near-miss rate. As a result, the need for complementary bronchoscopic guidance that provides real-time feedback on the correct positioning of the biopsy instruments is urgent.
Needle-based Confocal laser endomicroscopy (nCLE) is a novel high-resolution imaging technique that uses an excitation laser light to create 'real-time' microscopic images of tissues. nCLE can be integrated into the biopsy needle, allowing real-time cancer detection at the tip of the biopsy needle during bronchoscopy. The confocal microscope captures autofluorescence of tissues or, combined with intravenously (IV) infused fluorophores (such as fluorescein) allows imaging of individual tumor cells. Recent studies on nCLE-imaging in lung tumors and metastatic lymph nodes have identified and validated nCLE criteria for malignancy (enlarged pleomorphic cells, dark clumps and directional streaming) and airway/lung parenchyma (alveoli, elastin fibres of the conducting airway, bronchial epithelium and still image) and granulomas. A recent study demonstrated that these nCLE-criteria can be used in real-time to fine-tune the needle positioning during ongoing bronchoscopy and thereby potentially improve the diagnostic yield.
This randomized controlled trials aims to evaluate the added value of nCLE-imaging (smart needle) to the conventional used bronchoscopic approach for peripheral lung lesion analysis.
Objective: This multicenter, randomized controlled trial, aims to investigate if nCLE-imaging integrated with conventional bronchoscopy results in a higher diagnostic yield compared to conventional bronchoscopy without nCLE in the diagnosis of peripheral lung nodules.
Study design: Investigator-initiated, international, multi-center randomized controlled trial including university and general hospitals.
Study population: Patients (>18 years old) with suspected malignant peripheral lung lesions with an indication for bronchoscopic analysis.
Procedure: Bronchoscopy will be performed according to institutional practice, including radial endobronchial ultrasound (r-EBUS) and optionally fluoroscopy, electromagnetic navigation, virtual bronchoscopy and/or ultrathin bronchoscopy. This is followed by transbronchial needle aspiration (TBNA) and (cryo-)biopsies (control arm). In the study arm, nCLE-imaging will be added prior to TBNA tissue acquisition to fine-tune the sampling area. Cytology staining for rapid onsite evaluation (ROSE) and cellblock will be performed according to local practice.
Primary objective:
To determine if the addition of nCLE-imaging to conventional bronchoscopic peripheral lung lesion analysis results in an improved diagnostic yield. (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis out of the total number of patients that have received the diagnostic bronchoscopic procedure).
- Being tested
- Neelde Based Confocal Laser Endomicroscopy, Conventional diagnostic bronchoscopy
- Keywords
- Confocal Microscopy, Bronchoscopy, Confocal laser endomicroscopy, CLE, Fluoroscopy
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neelde Based Confocal Laser EndomicroscopyDevice
Confocal microscopy through the TBNA needle before tissue sampling using the Cellvizio system and AQ flex probe (Mauna Kea Technologies)
Conventional diagnostic bronchoscopyProcedure or surgery
Conventional diagnostic bronchoscopy with r-EBUS and optionally fluoroscopy AND/OR EMN AND/OR VB AND/OR ultrathin scope
| Study group | Role | What they receive |
|---|---|---|
| nCLE arm | Experimental | Diagnostic bronchoscopy is done according to institutional practice with the addition of nCLE Receives: Device: Neelde Based Confocal Laser Endomicroscopy; Procedure: Conventional diagnostic bronchoscopy |
| Control arm | Active comparator | Diagnostic bronchoscopy is done according to institutional practice without the addition of nCLE Receives: Procedure: Conventional diagnostic bronchoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic yield (intermediate definition)
Diagnostic yield (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis [either malignant, specific benign or non-specific benign confirmed as benign in follow-up], relative to the total number of patients that underwent the diagnostic bronchoscopic procedure). If patients with multiple lesions are included, the diagnostic yield will be computed per nodule.
Measured: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Secondary outcomes (13)
Diagnostic sensitivity
Diagnostic sensitivity for malignancy (defined as the proportion of patients in whom the bronchoscopic procedure diagnoses malignancy relative to the total number of patients with a final diagnosis of malignancy as determined by the reference standard).
Measured: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield (strict definition)
Diagnostic yield according to the strict definition by Vachani et al.(21) (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis [either malignant or specific benign diagnosis], relative to the total number of patients that underwent the diagnostic bronchoscopic procedure).
Measured: After all patients have been included (expected total time frame 2 years)
Procedure duration
Procedure duration (from bronchoscope insertion until removal).
Measured: During procedure (bronchoscopy)
Proportion needle repositionings and fine-tuning
Percentage of patients in which the needle was fine-tuned (defined as moving the needle within the same distal airway) or repositioned (defined as the selection of a different distal airway for tissue sampling) based on nCLE feedback (defined as the number of patients the needle was fine-tuned/repositioned divided by the total number of patients in which nCLE imaging was used).
Measured: During procedure (bronchoscopy)
Fluoroscopy time/dose
Fluoroscopy radiation time and dose.
Measured: During procedure (bronchoscopy)
Yield ROSE
Diagnostic yield of ROSE (defined as the proportion of patients in whom ROSE resulted in a classifying diagnosis [malignant or specific benign diagnosis], relative to the total number of patients).
Measured: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
ROSE tool-in-lesion
Proportion of patients in which ROSE provided tool-in-lesion confirmation, meaning that the acquired tissue shows signs of a malignant or non-malignant diagnosis and was not related to airway/lung parenchyma sampling such as bronchus epithelium/blood contamination, and tissue not suitable for a specific diagnosis such as atypical cells.
Measured: During procedure (bronchoscopy)
Complication rate
Complication rate (defined as any complication or complication categories occurring during or directly after the bronchoscopic procedure or any procedure-related complication within one week after the procedure).
Measured: Up to 1 week after bronchoscopy
Additional diagnostics needed
Requirement of additional diagnostic procedures (CT-guided transthoracic biopsies, surgical diagnostics and/or additional bronchoscopy) during the 6-month follow-up period.
Measured: Up to 6 months after index bronchoscopy
Diagnostic yield subgroup analysis (stratified by lesion size in mm)
To assess the diagnostic yield (primary outcome) for two subgroups (≤20 mm vs >20 mm)
Measured: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield subgroup analysis (stratified rEBUS visibility)
To assess the diagnostic yield (primary outcome) for three subgroups (eccentric vs concentric vs absent)
Measured: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield subgroup analysis (stratified by location in the lung)
To assess the diagnostic yield (primary outcome) for three subgroups (upper lobe (without lingual) vs middle lobe/lingual vs lower lobe)
Measured: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield subgroup analysis (stratified by Brock score)
To assess the diagnostic yield (primary outcome) for three subgroups (Brock score <10%, 10 - 35%, 36-70% and >70%)
Measured: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2023
- Study start18 Oct 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 208 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
- Sponsor type
- University, hospital or other
- Collaborators
- Mauna Kea Technologies
- Responsible party
- Principal investigator, Prof. J.T. Annema, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Jouke Annema, Prof. dr., Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06079970
- Sponsor's protocol ID
- NL83267.018.22
- Acronym
- CLEVER
- Status last verified
- Apr 2025
- First submitted
- 2 Oct 2023
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: All data relevant to the study will be included in the article or uploaded as supplementary information. Data requests can be submitted to the researchers at the Amsterdam UMC, Amsterdam, The Netherlands.
Publications
Wijmans L, Yared J, de Bruin DM, Meijer SL, Baas P, Bonta PI, Annema JT. Needle-based confocal laser endomicroscopy for real-time diagnosing and staging of lung cancer. Eur Respir J. 2019 Jun 20;53(6):1801520. doi: 10.1183/13993003.01520-2018. Print 2019 Jun.
PubMed 31023849Kramer T, Wijmans L, van Heumen S, Bansal S, Jeannerat D, Manley C, de Bruin M, Bonta PI, Annema JT. Needle-based confocal laser endomicroscopy for real-time granuloma detection. Respirology. 2023 Oct;28(10):934-941. doi: 10.1111/resp.14542. Epub 2023 Aug 10.
PubMed 37562791Manley CJ, Kramer T, Kumar R, Gong Y, Ehya H, Ross E, Bonta PI, Annema JT. Robotic bronchoscopic needle-based confocal laser endomicroscopy to diagnose peripheral lung nodules. Respirology. 2023 May;28(5):475-483. doi: 10.1111/resp.14438. Epub 2022 Dec 19.
PubMed 36535801Kramer T, Wijmans L, de Bruin M, van Leeuwen T, Radonic T, Bonta P, Annema JT. Bronchoscopic needle-based confocal laser endomicroscopy (nCLE) as a real-time detection tool for peripheral lung cancer. Thorax. 2022 Apr;77(4):370-377. doi: 10.1136/thoraxjnl-2021-216885. Epub 2021 Jun 25.
PubMed 34172559Vachani A, Maldonado F, Laxmanan B, Kalsekar I, Murgu S. The Impact of Alternative Approaches to Diagnostic Yield Calculation in Studies of Bronchoscopy. Chest. 2022 May;161(5):1426-1428. doi: 10.1016/j.chest.2021.08.074. Epub 2021 Sep 7. No abstract available.
PubMed 34506792van Heumen S, Kramer T, Korevaar DA, Gompelmann D, Bal C, Hetzel J, Jahn K, Poletti V, Ravaglia C, Sadoughi A, Stratakos G, Bakiri K, Koukaki E, Anagnostopoulos N, Votruba J, Sestakova Z, Heuvelmans MA, Daniels JMA, de Bruin DM, Bonta PI, Annema JT. Bronchoscopy with and without needle-based confocal laser endomicroscopy for peripheral lung nodule diagnosis: protocol for a multicentre randomised controlled trial (CLEVER trial). BMJ Open. 2024 Jul 4;14(7):e081148. doi: 10.1136/bmjopen-2023-081148.
PubMed 38964802
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bronchoscopy With and Without Needle-based Confocal Laser Endomicroscopy for Peripheral Lung Nodule Diagnosis: Protocol for a Multicenter Randomized Controlled Trial (CLEVER Trial)
- ClinicalTrials.gov ID
- NCT06079970
- Acronym / sponsor ID
- CLEVER / NL83267.018.22
- Keywords
- Confocal Microscopy, Bronchoscopy, Confocal laser endomicroscopy, CLE, Fluoroscopy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 208 participants (estimated)
- Lead sponsor
- Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)University, hospital or other
- Collaborators
- Mauna Kea Technologies
- Study start
- 18 Oct 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 12 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this multi-center randomized clinical trial is to evaluate the added value of needle based confocal laser endomicroscopy (nCLE)-imaging to regular diagnostic bronchoscopic peripheral lung lesion analysis on the diagnostic yield in patients with peripheral pulmonary nodules suspect for malignancy.
The main question[s] it aims to answer are:
To determine if the addition of nCLE-imaging to conventional diagnostic bronchoscopic peripheral lung lesion analysis results in an improved diagnostic yield (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis out of the total number of patients that have received the diagnostic bronchoscopic procedure).
Participants will undergo diagnostic bronchoscopy either with or without the addition of nCLE imaging before each TBNA. Based on the feedback of the CLE images on (in)correct placement of the needle, the needle might be repositioned before sampling. Comparison between the diagnostic yield of these groups will be done including subgroup analysis.
Detailed description
Rationale: Lung cancer screening and the increasing use of chest-computed tomography (CT) has led to an increase in the number of (incidental) found suspected malignant lung lesions. Since tissue acquisition for pathological analysis is prerequisite for diagnosis and optimal treatment, a drastic increase in the number of patients that need to undergo bronchoscopy is expected.
Over 70% of the suspected lesions develop in the periphery of the lung and are therefore not visible during conventional bronchoscopy. Although several bronchoscopic navigational techniques demonstrated an improved navigation towards the target lesion, the diagnostic yield remains suboptimal due to a substantial near-miss rate. As a result, the need for complementary bronchoscopic guidance that provides real-time feedback on the correct positioning of the biopsy instruments is urgent.
Needle-based Confocal laser endomicroscopy (nCLE) is a novel high-resolution imaging technique that uses an excitation laser light to create 'real-time' microscopic images of tissues. nCLE can be integrated into the biopsy needle, allowing real-time cancer detection at the tip of the biopsy needle during bronchoscopy. The confocal microscope captures autofluorescence of tissues or, combined with intravenously (IV) infused fluorophores (such as fluorescein) allows imaging of individual tumor cells. Recent studies on nCLE-imaging in lung tumors and metastatic lymph nodes have identified and validated nCLE criteria for malignancy (enlarged pleomorphic cells, dark clumps and directional streaming) and airway/lung parenchyma (alveoli, elastin fibres of the conducting airway, bronchial epithelium and still image) and granulomas. A recent study demonstrated that these nCLE-criteria can be used in real-time to fine-tune the needle positioning during ongoing bronchoscopy and thereby potentially improve the diagnostic yield.
This randomized controlled trials aims to evaluate the added value of nCLE-imaging (smart needle) to the conventional used bronchoscopic approach for peripheral lung lesion analysis.
Objective: This multicenter, randomized controlled trial, aims to investigate if nCLE-imaging integrated with conventional bronchoscopy results in a higher diagnostic yield compared to conventional bronchoscopy without nCLE in the diagnosis of peripheral lung nodules.
Study design: Investigator-initiated, international, multi-center randomized controlled trial including university and general hospitals.
Study population: Patients (>18 years old) with suspected malignant peripheral lung lesions with an indication for bronchoscopic analysis.
Procedure: Bronchoscopy will be performed according to institutional practice, including radial endobronchial ultrasound (r-EBUS) and optionally fluoroscopy, electromagnetic navigation, virtual bronchoscopy and/or ultrathin bronchoscopy. This is followed by transbronchial needle aspiration (TBNA) and (cryo-)biopsies (control arm). In the study arm, nCLE-imaging will be added prior to TBNA tissue acquisition to fine-tune the sampling area. Cytology staining for rapid onsite evaluation (ROSE) and cellblock will be performed according to local practice.
Primary objective:
To determine if the addition of nCLE-imaging to conventional bronchoscopic peripheral lung lesion analysis results in an improved diagnostic yield. (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis out of the total number of patients that have received the diagnostic bronchoscopic procedure).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| nCLE arm | Experimental | Device: Neelde Based Confocal Laser Endomicroscopy, Procedure: Conventional diagnostic bronchoscopyDiagnostic bronchoscopy is done according to institutional practice with the addition of nCLE |
| Control arm | Active comparator | Procedure: Conventional diagnostic bronchoscopyDiagnostic bronchoscopy is done according to institutional practice without the addition of nCLE |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- ≥18 years of age
- Suspected malignant peripheral lung lesion with an indication for a bronchoscopic diagnostic work-up as determined by the attending physician or tumor board. Peripheral pulmonary lesions are defined as lesions located beyond the visible segmental bronchi, not detectable by regular flexible bronchoscopy
- Bronchus sign on pre-procedural CT or estimated confidence for successful navigation to the nodule resulting in a r-EBUS signal
- Solid part of the lesion must be ≧10 mm
- Largest dimension of lesion size on CT ≦30 mm (long-axis)
Key exclusion criteria (11 listed)
- Inability or non-willingness to provide informed consent
- Endobronchial visible malignancy on bronchoscopic inspection
- Target lesion within reach of the linear EBUS scope
- Failure to comply with the study protocol
- Known allergy or risk factors for an allergic reaction to fluorescein
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neelde Based Confocal Laser EndomicroscopyConfocal microscopy through the TBNA needle before tissue sampling using the Cellvizio system and AQ flex probe (Mauna Kea Technologies) | Device | nCLE arm |
| Conventional diagnostic bronchoscopyConventional diagnostic bronchoscopy with r-EBUS and optionally fluoroscopy AND/OR EMN AND/OR VB AND/OR ultrathin scope | Procedure or surgery | Control arm, nCLE arm |
Primary outcome
Diagnostic yield (intermediate definition)
Time frame: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis [either malignant, specific benign or non-specific benign confirmed as benign in follow-up], relative to the total number of patients that underwent the diagnostic bronchoscopic procedure). If patients with multiple lesions are included, the diagnostic yield will be computed per nodule.
13 secondary outcomes
Diagnostic sensitivity
Time frame: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield (strict definition)
Time frame: After all patients have been included (expected total time frame 2 years)
Procedure duration
Time frame: During procedure (bronchoscopy)
Proportion needle repositionings and fine-tuning
Time frame: During procedure (bronchoscopy)
Fluoroscopy time/dose
Time frame: During procedure (bronchoscopy)
Yield ROSE
Time frame: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
ROSE tool-in-lesion
Time frame: During procedure (bronchoscopy)
Complication rate
Time frame: Up to 1 week after bronchoscopy
Additional diagnostics needed
Time frame: Up to 6 months after index bronchoscopy
Diagnostic yield subgroup analysis (stratified by lesion size in mm)
Time frame: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield subgroup analysis (stratified rEBUS visibility)
Time frame: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield subgroup analysis (stratified by location in the lung)
Time frame: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Diagnostic yield subgroup analysis (stratified by Brock score)
Time frame: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Background: PubMed 31023849Wijmans L, Yared J, de Bruin DM, Meijer SL, Baas P, Bonta PI, Annema JT. Needle-based confocal laser endomicroscopy for real-time diagnosing and staging of lung cancer. Eur Respir J. 2019 Jun 20;53(6):1801520. doi: 10.1183/13993003.01520-2018. Print 2019 Jun.
- Background: PubMed 37562791Kramer T, Wijmans L, van Heumen S, Bansal S, Jeannerat D, Manley C, de Bruin M, Bonta PI, Annema JT. Needle-based confocal laser endomicroscopy for real-time granuloma detection. Respirology. 2023 Oct;28(10):934-941. doi: 10.1111/resp.14542. Epub 2023 Aug 10.
- Background: PubMed 36535801Manley CJ, Kramer T, Kumar R, Gong Y, Ehya H, Ross E, Bonta PI, Annema JT. Robotic bronchoscopic needle-based confocal laser endomicroscopy to diagnose peripheral lung nodules. Respirology. 2023 May;28(5):475-483. doi: 10.1111/resp.14438. Epub 2022 Dec 19.
- Background: PubMed 34172559Kramer T, Wijmans L, de Bruin M, van Leeuwen T, Radonic T, Bonta P, Annema JT. Bronchoscopic needle-based confocal laser endomicroscopy (nCLE) as a real-time detection tool for peripheral lung cancer. Thorax. 2022 Apr;77(4):370-377. doi: 10.1136/thoraxjnl-2021-216885. Epub 2021 Jun 25.
- Background: PubMed 34506792Vachani A, Maldonado F, Laxmanan B, Kalsekar I, Murgu S. The Impact of Alternative Approaches to Diagnostic Yield Calculation in Studies of Bronchoscopy. Chest. 2022 May;161(5):1426-1428. doi: 10.1016/j.chest.2021.08.074. Epub 2021 Sep 7. No abstract available.
- Derived from this study: PubMed 38964802van Heumen S, Kramer T, Korevaar DA, Gompelmann D, Bal C, Hetzel J, Jahn K, Poletti V, Ravaglia C, Sadoughi A, Stratakos G, Bakiri K, Koukaki E, Anagnostopoulos N, Votruba J, Sestakova Z, Heuvelmans MA, Daniels JMA, de Bruin DM, Bonta PI, Annema JT. Bronchoscopy with and without needle-based confocal laser endomicroscopy for peripheral lung nodule diagnosis: protocol for a multicentre randomised controlled trial (CLEVER trial). BMJ Open. 2024 Jul 4;14(7):e081148. doi: 10.1136/bmjopen-2023-081148.
- Individual participant dataSharing planned: Yes. All data relevant to the study will be included in the article or uploaded as supplementary information. Data requests can be submitted to the researchers at the Amsterdam UMC, Amsterdam, The Netherlands.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jouke Annema, Prof. dr. contact
Jouke Annema, Prof. dr. principal investigator
Amsterdam UMC
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neelde Based Confocal Laser Endomicroscopy and Conventional diagnostic bronchoscopy in people with Lung Cancer and Lung Neoplasm Malignant, run by Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC) at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Austria, Czechia, Greece, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Saskia van Heumen, MSc (+31(0)20 566 2694, s.vanheumen@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic yield (intermediate definition) (time frame: After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06079970, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.